Transcriptional Mediators Kto and Skd Are Involved in the Regulation of the IMD Pathway and Anti-<em>Plasmodium</em> Defense in <em>Anopheles gambiae</em>

<div><p>The malarial parasite <em>Plasmodium</em> must complete a complex lifecycle in its <em>Anopheles</em> mosquito host, the main vector for <em>Plasmodium</em>. The mosquito resists infection with the human malarial parasite <em>P. falciparum</em> by engaging the NF-κB immune signaling pathway, IMD. Here we show that the conserved transcriptional mediators Kto and Skd are involved in the regulation of the mosquito IMD pathway. RNAi-mediated depletion of Kto and Skd in the <em>Anopheles gambiae</em> cell line L5-3 resulted in a decrease in the transcript abundance of <em>Cec1,</em> which is controlled by the IMD pathway. Silencing the two genes also resulted in an increased susceptibility of the mosquito to bacterial and <em>Plasmodium falciparum</em> infection, but not to infection with the rodent malaria parasite <em>P. berghei</em>. We also showed that Kto and Skd are not transcriptional co-activators of Rel2 or other key factors of the IMD pathway; however, they participate in the regulation of the IMD pathway, which is crucial for the mosquito’s defense against <em>P. falciparum</em>.</p>